Dresden 2020 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 23: Focus: Physics of Stem Cells

BP 23.5: Vortrag

Mittwoch, 18. März 2020, 11:30–11:45, ZEU 250

Robustness and timing of cellular differentiation through population based symmetry-breaking — Angel Stanoev, Dhruv Raina, Christian Schröter, and •Aneta Koseska — Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund

During mammalian development, cell types expressing mutually exclusive genetic markers are iteratively differentiated from a multilineage primed state. The current dynamical framework of differentiation, single-cell multistability, however requires that initial conditions in the multilineage primed state are appropriately controlled to result in robust proportions of differentiated fates.

We propose a fundamentally different dynamical treatment in which cellular identities emerge and are maintained on population level, as a novel unique solution of the coupled system. We show that the subcritical organization of such a coupled system close to the bifurcation point enables symmetry-breaking to be triggered by cell number increase in a timed, self-organized manner. Robust cell type proportions are thereby an inherent feature of the resulting inhomogeneous solution. In accordance with this theory, we demonstrate experimentally that a population-based mechanism governs cell differentiation in an embryonic stem cell model for an early lineage decision of mammalian embryogenesis. Our results therefore suggest that robustness and accuracy can emerge from the cooperative behavior of growing cell populations during development.